The present invention relates to a system for regulation of fluid flow and more specifically to a system that can pump liquid from a vented container and deliver the liquid at a pulse free flow to an instrument.
Flow analysis has been used in research and clinical applications to analyze the characteristics of particulate targets. In this system a particle stream is injected into the center of a sheath flow stream. The resulting laminar flow is passed through an optical detection location, where the stream is illuminated and fluorescence and/or light scatter is measured from passing target particles. In sorting analyzers, the flow stream may subsequently divided into droplets, with targeted particles separated into droplets. These droplets could then be sorted to recover the particle of interest.
The requirements of a robust sheath flow delivery system are a) that it provides an adequate flow capacity and b) that it present a negligibly small temporal flow variation. The flow variation is especially important for sorting application. During a sorting operation a target is analyzed and identified at a first location, droplets are generated downstream at a second location, droplets are tagged for sorting at a third downstream location (generally by applying a charge to the droplet), and droplets are sorted at a fourth downstream location (e.g. by passing charged droplets between charged plates). The first through fourth locations are separated along a flow path. Sorting of droplets requires precise correspondence between target recognition, droplet generation, and droplet charging and deflection. If fluid velocity varies in pulses, such coordination of events becomes extremely difficult.
The sheath flow liquid used in flow cytometry is generally a phosphate buffered saline or other isotonic solution. In prior flow analysis systems, a pressurized reservoir was used to supply the flow stream. A regulator provides a static air pressure over the free surface of the sheath flow fluid within a large, rigid tank. For high pressure systems this tank would usually be a stainless steel pressurized tank. For lower pressure applications the tank would be made of reinforced plastic. The pressure in the tank drives the fluid in the tank to an outlet tube leading to the flow analysis cell.
In such large tank systems the pressure head over sheath flow liquid within a tank is varied to compensate for pressure loss as fluid level in the tank decreases. Because the flow volume requirement of the cytometer is small compared to the volume within the tank, the pressure variation associated with volume change is gradual. It is fairly easy for a pressure regulator to vary the pressure within the tank to compensate for the pressure change caused by the declining fluid level within the tank.
There are a number of drawbacks to this system. First, the system is bulky and expensive. Second, this system is relatively difficult to use. Manipulation of the large, heavy sheath flow tanks is cumbersome. Third, the system lacks flexibility. To add or exchange the sheath flow fluid the tank must be depressurized, supply lines disconnected, the tank refilled (or emptied and refilled) and repressurized. This results in system down time and requires some expertise to insure consistency in system performance. In many present systems, the pressure regulator does not automatically compensate for pressure variation associated with changes in the tank fluid level. Instead the operator must adjust the regulator pressure periodically as the level in the sheath tank changes. This requires operator time and could result in error.
Different solutions providing a method to generate a pulse free pumping from a vented container have been proposed. U.S. Pat. No. 6,227,807 discloses a means for controlling the output flow of a pump. The radial speed of the pump is controlled during discreet segments of the motor""s radial path during pump revolutions. This is performed by a memory, counter and amplifier. These control the speed of the pump stepper motor at discrete points in the pump cycle. The down stroke time is minimized and a flow interruption filter suppresses the interruption of the flow during the upstroke.
U.S. Pat. Nos. 6,017,194 and 6,200,101 disclose a method and apparatus for providing consistent liquid pressure output. In this device, liquid is pumped from a vented container by a pump into a liquid accumulator. A volume sensor of fluid within the accumulator is used to control the pump such that liquid within the accumulator is maintained at a constant height. The negative spring rate of the accumulator piston is equal to the sum of the positive spring rates of the accumulator control spring, diaphragm piston, and flexure support sensor lever. The flexure support sensor lever moves the accumulator diaphragm, which triggers a signal to the pump. This feedback loop regulates pump speed to maintain a constant level of liquid within a liquid accumulator.
While these solutions allow for pumping from a vented container, alternative methods of producing a uniform pump flow would be desirable.
It is an object of the invention to provide a flow system that provides a constant flow. This system should be supplied from a user selected, nonpressurized container. It should not be affected by the level of fluid level in this nonpressurized container.
It is a further object to provide such a system having lower material requirements. Such a system would have a lower weight and a smaller bench space requirement.
It is a further object of the invention to provide a system that requires less precise pump control and is adaptable for use with available pulsile pumps.
These objects have been achieved through a sheath supply system that uses a pump to draw liquid from a non-pressurized container and pump this liquid into a supply line which empties into an attenuation chamber. Liquid flows from an outlet in the attenuation chamber to the plenum chamber through a tube. At least one orifice restricts the diameter of flow between the pump and the plenum chamber. The combination of the attenuation chamber and the orifice act as a first shock wave dampener for pump pulses.
Liquid flows through the orifice into a plenum chamber. Liquid within this chamber is maintained at a specific height within the chamber. A pressure transducer regulates the pressure head over this liquid. The height of liquid within the chamber, as determined by a sensor, is regulated by turning the pump on and off. This plenum chamber acts as a second wave shock absorber, further attenuating pulses in fluid flow. At the bottom of the plenum chamber is an outlet, which leads to an analytical system such as a flow cytometer, blood analyzer, or other device requiring a constant fluid flow at a constant pressure and conditioned to substantially pulse free.